This application proposes to examine and compare the effects of spontaneous and surgically induced hypertension on cardiac structure at various stages throughout the time course of hypertension. The prevention and reversal of cardiac hypertrophy by antihypertensive drug therapy will also be studied. The percentage volume distribution of cardiac muscle, connective tissue and vasculature components will be calculated using computerized quantitative morphological techniques at the light and electron microscopy levels. These data will be correlated with actual measurements of myocyte cell size obtained from SEM of isolated myocytes. The possible role of hyperplasia and hyperploidy, and multi-nuclearity in cardiac hypertrophy will also be examined using autoradiography and quantitative feulgen techniques, respectively. In these studies, particular emphasis will be placed on the early pre-hypertensive stages in spontaneously-hypertensive animals, but will also be compared with similar data from renal hypertensive rats. Lastly, the possibility of pathological ultrastructural changes in rats treated with Captopril and hydrochlorothiazide will be examined to confirm results of a pilot study. The results of these studies will provide quantitative morphological data to describe the time course of, and tissue elements contributing to cardiac hypertrophy, as well as the efficacy and morphological target of various antihypertensive drugs in reversal or prevention of structural hypertrophy. The data will be integrated with ongoing biochemical studies on the same model systems. The overall objective of these studies will be to quantitatively appraise structural changes at the tissue level with those at the cellular and subcellular level, and to examine nuclear DNA changes to provide structural correlates of functional alterations previously shown using biochemical techniques.